The present invention relates to a novel MRI contrast approach for imaging of tissue and in particular ablated tissue.
Various MRI techniques are used to obtain contrast between different tissues as well as between normal and pathological states of same tissues. Examples are: T1 and T2 weighted, proton density, diffusion weighted and MTC, each being used for different imaging and diagnostic purposes.
Utilizing imaging modalities to evaluate damage done to a surgical ablation target and to tissues near a surgical ablation target is an essential aspect of many surgical techniques. Tissue damage evaluation is typically done both during surgical use of thermal ablation procedures and subsequent to such use. Yet accurate evaluation of tissue damage is difficult to achieve. None of the MRI techniques listed above enables direct visualization of tissue damage, nor enables to distinguish between coagulated and non-coagulated tissues.
Thermal ablation techniques include heating techniques such as heating with RF energy, with microwave energy, with focused ultrasound, and with laser light, and cooling techniques such as evaporative cryoablation and Joule-Thomson cryoablation. Monitoring of the effects of application of these techniques is typically accomplished indirectly, by measuring tissue temperatures. Yet even in the case of those thermal therapy techniques which enable incorporation of use of thermometers and thermocouples during procedures, temperature is measured only at discrete points, such as at the operating tips of thermometers, and therefore does not provide an accurate indication of temperature throughout the affected tissue. Consequently, MRI is a preferred method for measuring tissue temperatures.
The most commonly used MRI methods for measuring temperature are the T1-weighted method and the proton resonance frequency (PRF) method.
The T1-weighted method is discussed by Dick, E. A., et al., MR-guided laser thermal ablation of primary and secondary liver tumours. Clin Radiol, 2003. 58(2): p. 112-20, by Fiedler, V. U., et al., Laser-induced interstitial thermotherapy of liver metastases in an interventional 0.5 Tesla MRI system: technique and first clinical experiences. J Magn Reson Imaging, 2001. 13(5): p. 729-37, by Morrison, P. R., et al., MRI of laser-induced interstitial thermal injury in an in vivo animal liver model with histologic correlation. J Magn Reson Imaging, 1998. 8(1): p. 57-63, and by Matsumoto, R., et al., Tissue temperature monitoring for thermal interventional therapy: comparison of T1-weighted MR sequences. J Magn Reson Imaging, 1994. 4(1): p. 65-70.
Proton resonance frequency (PRF) methods are discussed by Palussiere, J., et al., Feasibility of MR-guided focused ultrasound with real-time temperature mapping and continuous sonication for ablation of VX2 carcinoma in rabbit thigh. Magn Reson Med, 2003. 49(1): p. 89-98, and by Weidensteiner, C., et al., Real-time NM temperature mapping of rabbit liver in vivo during thermal ablation. Magn Reson Med, 2003. 50(2): p. 322-30.
MRI methods for temperature measurement suffer from a variety of drawbacks and limitations. These include the following:
(1) Spin-echo sequences cannot be used for PRF methods since the temperature-induced phase contribution will be refocused. Optimal TE for PRF is equal to T2*, as discussed by de Zwart, J. A., et al., Fast magnetic-resonance temperature imaging. J Magn Reson B, 1996. 112(1): p. 86-90. For tissues with short T2*(such as the liver) the method is difficult to perform and the signal-to-noise ratio is small, as discussed in Weidensteiner, C., et al., Stability of real-time MR temperature mapping in healthy and diseased human liver. J Magn Reson Imaging, 2004. 19(4): p. 438-46.
(2) Temperature-dependent changes in magnetic susceptibility and conductivity contribute to errors in PRF. These factors are discussed in Peters, R. D., R. S. Hinks, and R. M. Henkelman, Heat-source orientation and geometry dependence in proton-resonance frequency shift magnetic resonance thermometry. Magn Reson Med, 1999. 41(5): p. 909-18, Peters, R. D. and R. M. Henkelman, Proton-resonance frequency shift MR thermometry is affected by changes in the electrical conductivity of tissue. Magn Reson Med, 2000. 43(1): p. 62-71, and in De Poorter, J., Noninvasive MRI thermometry with the proton resonance frequency method: study of susceptibility effects. Magn Reson Med, 1995. 34(3): p. 359-67.
(3) The PRF method suffers from motion artifacts, as discussed in Fiedler op. cit. PRF is based on the phase difference between two complex gradient-echo MR images, and thus is sensitive to motion artifacts in mobilized organs and tissues, such as the liver. See also Rieke, V., et al., Referenceless PRF shift thermometry. Magn Reson Med, 2004. 51(6): p. 1223-31.
(4) PRF thermometry can be applied usefully only in mid or high field (≧1 T). See Germain, D., et al., MR monitoring of tumour thermal therapy. Magma, 2001. 13(1): p. 47-59, and Quesson, B., J. A. de Zwart, and C. T. Moonen, Magnetic resonance temperature imaging for guidance of thermotherapy. J Magn Reson Imaging, 2000. 12(4): p. 525-33.
(5) T1 is sensitive to coagulation also, therefore giving inaccurate estimation of temperature as necrosis develops, when using T1 weighted sequences. This problem is discussed in Graham, S. J., M. J. Bronskill, and R. M. Henkelman, Time and temperature dependence of MR parameters during thermal coagulation of ex vivo rabbit muscle. Magn Reson Med, 1998. 39(2): p. 198-203.
In addition to the above-noted limitations in accuracy and practicality of MRI temperature measurement, it may further be noted that once temperatures have been measured using T1-weighted or proton resonance frequency techniques, the extent of damage to examined tissue can only be roughly inferred or estimated by calculation based on the temperature. Tissue damage estimations based on such calculations are thus intrinsically indirect and necessarily somewhat inaccurate. These calculation methods are discussed in Graham, S. J., et al., Quantifying tissue damage due to focused ultrasound heating observed by MRI, Magn Reson Med, 1999. 41(2): p. 321-8, and Ishihara, Y., et al., A precise and fast temperature mapping using water proton chemical shift, Magn Reson Med, 1995. 34(6): p. 814-23.
In sum, estimation of damage to tissue on the basis of the temperature measurement suffers from inherent inaccuracies, and is susceptible to variations from one patient to another.
Thus, there is a widely recognized need for, and it would be highly advantageous to have, a method of directly measuring physical changes brought about in ablated tissue by thermal ablation.
It is further noted that currently popular methods for evaluating results of thermal therapies use T2-weighted and gadolinium contrast enhanced T1-weighted MR lesion images as a predictor of eventual cell death. This technique is discussed in Breen M S, Lazebnik R S, Fitzmaurice M, Nour S G, Lewin J S, Wilson D L. Radiofrequency thermal ablation: correlation of hyperacute MR lesion images with tissue response. J Magn Reson Imaging 2004; 20(3):475-486. For clinical treatments of patients with liver tumors, Vogl. et al. used contrast enhanced FLASH 2d sequences to give information about size of the coagulated tissue. This process also includes the injection of contrast agent, as discussed in Vogl T J, Mack M G, Muller P K, Straub R, Engelmann K, Eichler K. Interventional MR: interstitial therapy. Eur Radiol 1999; 9(8):1479-1487. Wacker et al. used gadolinium enhanced T1 weighted imaging for the follow stage, as discussed in Wacker F K, Reither K, Ritz J P, Roggan A, Germer C T, Wolf K J. MR-guided interstitial laser-induced thermotherapy of hepatic metastasis combined with arterial blood flow reduction: technique and first clinical results in an open MR system. J Magn Reson Imaging 2001; 13(1):31-36.
However, injections of gadolinium and similar contrast agents are invasive procedures and are therefore generally disadvantageous and may in some cases be specifically contra-indicated because of existing clinical conditions. Thus, there is a widely recognized need for, and it would be highly advantageous to have, a method of directly measuring physical changes brought about in ablated tissue by thermal ablation without necessitating injection of contrast agents into the body.